Systems and methods for vascular diagnosis using blood flow magnitude and/or direction

ABSTRACT

Systems and methods are disclosed for diagnosing and treatment planning for vascular steal syndromes and retrograde flow. One method includes receiving a reference blood flow direction at a location in a reference vasculature; determining a patient-related blood flow direction at a location in a patient&#39;s vasculature corresponding to the location in the reference vasculature; determining a difference in direction, between the reference blood flow direction of the reference vasculature and the patient-related blood flow direction of the patient&#39;s vasculature; and generating a representation of the location in the patient&#39;s vasculature associated with the difference in direction between the reference blood flow direction and the patient-related blood flow direction, or generating a treatment recommendation for the patient&#39;s vasculature based on the difference in direction between the reference blood flow direction and the patient-related blood flow direction.

RELATED APPLICATION(S)

This application claims priority to U.S. Provisional Application No.62/110,817 filed Feb. 2, 2015, the entire disclosure of which is herebyincorporated herein by reference in its entirety.

FIELD OF THE DISCLOSURE

Various embodiments of the present disclosure relate generally todisease assessment, treatment planning, and related methods. Morespecifically, particular embodiments of the present disclosure relate tosystems and methods for diagnosing or performing treatment planning forvascular steal syndromes and/or retrograde flow.

BACKGROUND

Blood flow may sometimes deviate from an expected pattern. One exampleof blood flow deviation may include retrograde flow, a condition where apatient's blood flow may change direction. Stenoses or valveregurgitation may contribute to retrograde flow. Another example ofblood flow deviation may include vascular steal syndromes, which mayinvolve medical complications that may cause flow to increase in onepart of the body at the expense of another. For example, vascularaccess-induced steal syndrome may include a condition where anarteriovenous (AV) fistula or graft may cause blood to flow through theaccess, “stealing” blood flow that would otherwise be delivered to theforearm or hand. Additional examples of these phenomena may include,e.g., subclavian steal syndrome, coronary steal syndrome, cardiac stealsyndrome, dialysis access steal syndrome, iliac steal syndrome,aorto-iliac steal syndrome, renal-splanchnic steal syndrome, mesentericarterial steal syndrome, splenic artery steal syndrome, and/orintersplanchnic steal syndrome.

Retrograde flow and vascular steal syndromes may be dangerous to apatient. For instance, a diversion of expected blood flow to tissue froma vascular steal syndrome may cause blood supply inefficiency to thattissue, which may then lead to necrosis. Retrograde flow may cause or belinked to ischemia.

Meanwhile, harmful, blood flow deviation-related conditions may be hardto detect in advance. For example, vascular steal syndromes may bedifficult to diagnose. Some vascular steal situations may occur onlyduring certain physiological states (e.g., coronary steal syndrome) orresult from moderate vascular disease. Thus, a desire exists to betterunderstand the various pathological situations in a patient'svasculature and how they may cause or contribute to vascular stealsyndromes or retrograde flow. More specifically, a desire exists fordiagnosis and treatment of vascular steal syndromes and retrograde flow.

Furthermore, treatments or medical procedures may be associated withblood flow deviance. In other words, treatments or medical proceduresperformed to improve a patient's health, may incidentally impair orendanger the patient's health due to the treatment's impact on thepatient's blood flow. For example, catheter flushing may causeretrograde flow and an arteriovenous (AV) fistula or graft may result ina vascular steal syndrome or retrograde blood flow. Thus, a desire alsoexists to identify a treatment that may resolve a flow deviance and/orhelp reduce or avoid a flow deviance. Specifically, a desire exists toensure that a treatment may effectively address a vascular stealsyndrome or, in the case of certain treatments (e.g., bypass graft),ensure that the treatment may not induce retrograde flow or a vascularsteal syndrome as a byproduct of treatment.

The foregoing general description and the following detailed descriptionare exemplary and explanatory only and are not restrictive of thedisclosure.

SUMMARY

According to certain aspects of the present disclosure, systems andmethods are disclosed for diagnosing and treatment planning for vascularsteal syndromes and/or retrograde flow.

One method includes: receiving a reference blood flow direction at alocation in a reference vasculature; determining a patient-related bloodflow direction at a location in a patient's vasculature corresponding tothe location in the reference vasculature; determining a difference indirection, between the reference blood flow direction of the referencevasculature and the patient-related blood flow direction of thepatient's vasculature; and generating a representation of the locationin the patient's vasculature associated with the difference in directionbetween the reference blood flow direction and the patient-related bloodflow direction, or generating a treatment recommendation for thepatient's vasculature based on the difference in direction between thereference blood flow direction and the patient-related blood flowdirection.

In accordance with another embodiment, a system for determining bloodflow deviation in a patient's vasculature comprises: a data storagedevice storing instructions for determining blood flow deviation in apatient's vasculature; and a processor configured for: receiving areference blood flow direction at a location in a reference vasculature;determining a patient-related blood flow direction at a location in apatient's vasculature corresponding to the location in the referencevasculature; determining a difference in direction, between thereference blood flow direction of the reference vasculature and thepatient-related blood flow direction of the patient's vasculature; andgenerating a representation of the location in the patient's vasculatureassociated with the difference in direction between the reference bloodflow direction and the patient-related blood flow direction, orgenerating a treatment recommendation for the patient's vasculaturebased on the difference in direction between the reference blood flowdirection and the patient-related blood flow direction.

In accordance with another embodiment, a non-transitory computerreadable medium for use on a computer system containingcomputer-executable programming instructions for performing a method ofdetermining blood flow deviation in a patient's vasculature, the methodcomprising: receiving a reference blood flow direction at a location ina reference vasculature; determining a patient-related blood flowdirection at a location in a patient's vasculature corresponding to thelocation in the reference vasculature; determining a difference indirection, between the reference blood flow direction of the referencevasculature and the patient-related blood flow direction of thepatient's vasculature; and generating a representation of the locationin the patient's vasculature associated with the difference in directionbetween the reference blood flow direction and the patient-related bloodflow direction, or generating a treatment recommendation for thepatient's vasculature based on the difference in direction between thereference blood flow direction and the patient-related blood flowdirection.

One method includes: receiving a reference relative blood flow magnitudecomparing blood flow magnitude at a first location versus a secondlocation in a reference vasculature; determining a first patient-relatedblood flow magnitude at a location in a patient's vasculaturecorresponding to the first location in the reference vasculature;determining a second patient-related blood flow magnitude at thelocation in a patient's vasculature corresponding to the second locationin the reference vasculature; determining a patient-related relativeblood flow magnitude by comparing the first patient-related blood flowmagnitude to the second patient-related blood flow magnitude; comparingthe reference relative blood flow magnitude and the patient-relatedrelative blood flow magnitude; and at least one of: generating arepresentation of the patient's vasculature based on the differencebetween the reference relative blood flow magnitude and thepatient-related relative blood flow magnitude, or generating a treatmentrecommendation for the patient's vasculature based on the differencebetween the reference relative blood flow magnitude and thepatient-related relative blood flow magnitude.

In accordance with another embodiment, a system for determining bloodflow deviation in a patient's vasculature comprises: a data storagedevice storing instructions for determining blood flow deviation in apatient's vasculature; and a processor configured for: receiving areference relative blood flow magnitude comparing blood flow magnitudeat a first location versus a second location in a reference vasculature;determining a first patient-related blood flow magnitude at a locationin a patient's vasculature corresponding to the first location in thereference vasculature; determining a second patient-related blood flowmagnitude at the location in a patient's vasculature corresponding tothe second location in the reference vasculature; determining apatient-related relative blood flow magnitude by comparing the firstpatient-related blood flow magnitude to the second patient-related bloodflow magnitude; comparing the reference relative blood flow magnitudeand the patient-related relative blood flow magnitude; and at least oneof: generating a representation of the patient's vasculature based onthe difference between the reference relative blood flow magnitude andthe patient-related relative blood flow magnitude, or generating atreatment recommendation for the patient's vasculature based on thedifference between the reference relative blood flow magnitude and thepatient-related relative blood flow magnitude.

In accordance with another embodiment, a non-transitory computerreadable medium for use on a computer system containingcomputer-executable programming instructions for performing a method ofdetermining blood flow deviation in a patient's vasculature, the methodcomprising: a reference relative blood flow magnitude comparing bloodflow magnitude at a first location versus a second location in areference vasculature; determining a first patient-related blood flowmagnitude at a location in a patient's vasculature corresponding to thefirst location in the reference vasculature; determining a secondpatient-related blood flow magnitude at the location in a patient'svasculature corresponding to the second location in the referencevasculature; determining a patient-related relative blood flow magnitudeby comparing the first patient-related blood flow magnitude to thesecond patient-related blood flow magnitude; comparing the referencerelative blood flow magnitude and the patient-related relative bloodflow magnitude; and at least one of: generating a representation of thepatient's vasculature based on the difference between the referencerelative blood flow magnitude and the patient-related relative bloodflow magnitude, or generating a treatment recommendation for thepatient's vasculature based on the difference between the referencerelative blood flow magnitude and the patient-related relative bloodflow magnitude.

Additional objects and advantages of the disclosed embodiments will beset forth in part in the description that follows, and in part will beapparent from the description, or may be learned by practice of thedisclosed embodiments. The objects and advantages of the disclosedembodiments will be realized and attained by means of the elements andcombinations particularly pointed out in the appended claims.

It is to be understood that both the foregoing general description andthe following detailed description are exemplary and explanatory onlyand are not restrictive of the disclosed embodiments, as claimed.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated in and constitute apart of this specification, illustrate various exemplary embodiments,and together with the description, serve to explain the principles ofthe disclosed embodiments.

FIG. 1A is an exemplary schematic depiction of vascular steal syndrome,according to an exemplary embodiment of the present disclosure.

FIG. 1B is a block diagram of an exemplary system and network diagnosingor performing treatment planning for vascular steal syndromes and/orretrograde flow, according to an exemplary embodiment of the presentdisclosure.

FIG. 2 is a block diagram of an exemplary method of diagnosing orperforming treatment planning for vascular steal syndromes and/orretrograde flow, according to an exemplary embodiment of the presentdisclosure.

FIG. 3A is a block diagram of an exemplary method of locating areas ofvascular steal syndromes and/or retrograde flow, according to anexemplary embodiment of the present disclosure.

FIG. 3B is a block diagram of an exemplary method of comparingtreatments related to vascular steal syndromes and/or retrograde flow,according to an exemplary embodiment of the present disclosure.

DESCRIPTION OF THE EMBODIMENTS

Reference will now be made in detail to the exemplary embodiments of thedisclosure, examples of which are illustrated in the accompanyingdrawings. Wherever possible, the same reference numbers will be usedthroughout the drawings to refer to the same or like parts.

Blood flow in the body may change or deviate from an expected pattern.Such deviations may be harmful to a patient, yet difficult to detect inadvance. For example, various pathological situations in a patient'svasculature may cause retrograde flow or vascular steal syndrome. Thismay mean, for instance, that the effect of vascular steal syndrome maynot arise, unless a patient is in a particular physiological state. Forexample, a patient with subclavian steal syndrome may suddenly faint ordevelop neurologic deficits when the patient is at a particularpathological state (e.g., during exercise), while the patient may appearnormal or healthy in other pathological conditions (e.g., at rest orduring moderate activity). The exemplary symptoms of fainting ordeveloping neurologic deficits may be caused by the way that blood isflowing due to the subclavian steal syndrome. Subclavian steal syndromeis described in more detail in FIG. 1A.

FIG. 1A is a schematic depiction of an exemplary vascular model 100 of apatient exhibiting a vascular steal syndrome, specifically, a subclaviansteal syndrome, according to an exemplary embodiment of the presentdisclosure. Vascular model 100 may include a vertebral artery 101 and asubclavian artery 103. The illustrated subclavian artery 103 may includean occlusion or proximal stenosis 105. A normal blood flow may flow fromthe vertebral artery 101, down through the portion of the subclavianartery 103 where the occlusion or proximal stenosis 105 is pictured.Subclavian steal syndrome may exist where blood flow 107 travels in the(retrograde) direction of the arm, rather than through the subclavianartery 103 in the direction of normal blood flow, i.e., toward thestenosis 105. In some cases, a blockage (e.g., occlusion or proximalstenosis 105) may cause the deviant blood flow 107. In other words, thearm, in this situation, “steals” blood from the flow of blood that isexpected to travel through the proximal subclavian artery for a normal,healthy patient.

Medical conditions that are expressed only during some pathologicalstates may be difficult to diagnose because occurrence is inconsistentand there is no way to measure blood flow deviation from blood vesselsor patient anatomy.

Therefore, an understanding of locations of deviant flow may beclinically important. The present disclosure may aid the diagnosis andtreatment of vascular steal syndromes and retrograde flow by identifyingarea(s) of a patient's vasculature with deviant flow magnitude and/ordirection. In addition, the present disclosure may provide systems andmethods for virtually exploring various treatment strategies. In thisway, the present disclosure provides systems and methods for identifyinga treatment that may resolve the flow deviancy. In one such embodiment,a comparison of various treatment strategies may be used to select anoptimal treatment that may resolve the flow deviancy.

FIG. 1B depicts a block diagram of an exemplary system 120 and networkfor diagnosing or performing treatment planning for vascular stealsyndromes and/or retrograde flow, according to an exemplary embodiment.Specifically, FIG. 1B depicts a plurality of physicians 122 and thirdparty providers 124, any of whom may be connected to an electronicnetwork 121, for example, the Internet, through one or more computers,servers, and/or handheld mobile devices. Physicians 122 and/or thirdparty providers 124 may create or otherwise obtain images of one or morepatients' anatomy. The physicians 122 and/or third party providers 124may also obtain any combination of patient-specific information, forexample, age, medical history, blood pressure, blood viscosity, patientactivity or exercise level, etc. Physicians 122 and/or third partyproviders 124 may transmit the anatomical images and/or patient-specificinformation to server systems 126 over the electronic network 121.Server systems 126 may include storage devices for storing images anddata received from physicians 122 and/or third party providers 124.Server systems 126 may also include processing devices for processingimages and data stored in the storage devices. For the presentdisclosure, “patient” may refer to any individual of interest.

FIG. 2 depicts a general embodiment of a method for diagnosing orperforming treatment planning for vascular steal syndromes and/orretrograde flow. For example, FIG. 2 includes a method for detectingretrograde flow or blood flow “stealing” that may occur in at least aportion of patient's circulatory system. FIGS. 3A and 3B include twomethods of displaying or processing results of the analysis in themethod of FIG. 2. For example, FIG. 3A depicts an embodiment of aprocess for locating areas of a patient's vasculature that may beassociated with detected retrograde flow or blood flow “stealing.”Locations in a patient's vasculature that may be associated with flowdeviation (or vascular steal syndrome/retrograde flow), may be relatedto effective treatment locations in the patient's vasculature. Forexample, the method of FIG. 3A may include recommending treatment at oneor more of the locations in the patient's vasculature associated withdeviant blood flow.

FIG. 3B depicts an embodiment of a process for comparing treatmentsrelated to vascular steal syndromes and/or retrograde flow. Aspreviously discussed, treatments may address, or in some cases evencause, one or more vascular steal syndromes and/or retrograde flow. Inone embodiment, the method of FIG. 3B may be used to assess a singletreatment. For example, the treatment may include a treatment forvascular steal syndrome or retrograde flow. In such a case, theassessment may include evaluating the treatment's efficacy in treatingthe patient's vascular steal syndrome or retrograde flow. In anotherinstance, the treatment may include a treatment for a condition, otherthan vascular steal syndrome or retrograde flow, that may impact thepatient. In such a case, the assessment may include evaluating thetreatment to determine the likelihood or risk that the treatment mayresult in vascular steal syndrome or retrograde flow for the patient.Furthermore, the method of FIG. 3B may be used to find an optimaltreatment for a patient, given the comparison of multiple treatments.Again, finding the optimal treatment may apply to the scenario ofselecting an optimal treatment for treating one or more blood flowdeviations, or the scenario of finding a treatment that has a lowerlikelihood of causing blood flow deviations that may harm the patient.The methods of FIGS. 3A and 3B may be performed together or separately.

FIG. 2 is a block diagram of an exemplary method 200 of diagnosing orperforming treatment planning for vascular steal syndromes and/orretrograde flow, according to an exemplary embodiment. The method ofFIG. 2 may be performed by server systems 126, based on information,images, and data received from physicians 122 and/or third partyproviders 124 over electronic network 121. Blood flow parameters (e.g.,blood flow magnitude and/or blood flow direction) may indicate, orimpact, a patient's health and medical condition. Method 200 may includea method of evaluating discrepancies between a patient's blood flow andhealthy blood flow to diagnose blood flow-related scenarios (e.g.,vascular steal syndromes and/or retrograde flow) and/or to informtreatment planning for such blood flow-related scenarios.

In one embodiment, step 201 may include receiving a patient-specificanatomical model including at least a portion of the patient'svasculature. In one embodiment, the patient-specific anatomic model mayhave been generated based on patient-specific imaging. Various imagingmodalities may provide patient anatomy for the anatomic model e.g.,computed tomography (CT) images (or scans), magnetic resonance imaging(MRI), ultrasound, angiography, etc. The imaging may includerepresentations of a patient's coronary vasculature, cerebralvasculature, peripheral vasculature, renal vasculature, or visceralvasculature. The patient-specific anatomical model may be received in anelectronic storage medium (e.g., hard drive, network drive, smart phone,tablet, cloud drive, etc.). For example, a third party vendor mayprovide the images. In one embodiment, the patient-specific anatomicalmodel may include, e.g., a 3D geometrical model (e.g., a triangulatedsurface mesh) of the patient's arterial vasculature or a 1D geometricalmodel of the patient's arterial vasculature. The modeled patientvasculature may include any vasculature in a patient's body, includingbut not limited to one or more of: coronary vasculature, cerebralvasculature, peripheral vasculature, renal vasculature, visceralvasculature, etc.

In one embodiment, step 203 may include receiving a physiological stateof the patient, e.g., a resting state, an exercise state, fasting, ahyperemic state, a postprandial, etc. The physiological state mayinclude a designated physiological state, for instance, a physiologicalstate at which the blood flow analysis of method 200 may take place. Inother words, the remaining steps of method 200 involving reference bloodflow or the patient's actual blood flow may relate to blood flow at thephysiological state received (e.g., designated) in step 203. Forexample, an exercise state may correspond to a reference blood flow andan actual patient blood flow higher than a resting state reference bloodflow or a resting state actual patient blood flow. Determining aphysiological state of the patient in a blood flow analysis may providecontext for a comparison of expected blood flow versus patient bloodflow, so that patient blood flow and reference blood flow are bloodflows associated with the same physiological state.

Furthermore, step 203 may permit comparison of blood flow deviations atvarious physiological states. For example, deviant flow may arise insome physiological states, and not in other physiological states.Identifying a physiological state as the basis of a blood flow analysismay permit comparison of blood flow characteristics from one state toanother. For instance, a comparison of healthy blood flow versus actual(e.g., patient) blood flow during a resting state may contrast from acomparison of healthy blood flow versus actual blood flow during anexercise state.

By extension, changes in physiological state may be observed from bloodflow. In one embodiment, step 203 may further include determining thephysiological state of the patient. For example, step 203 may includeidentifying or defining one or more physiological states and determiningthat the patients physical condition is associated with one or more ofthe identified or defined physiological states. In such a case, step 203may further include selecting a physiological state for the patient,based on the physiological state(s) determined to be associated with thepatient physical condition.

In one embodiment, step 205 may include receiving and/or determining areference blood flow. In one embodiment, receiving the reference bloodflow may include determining (e.g., estimating or measuring) thereference blood flow. For example, the reference blood flow may includean estimate of blood flow at one or more locations in thepatient-specific anatomical model, at one anatomical/disease state, orat a physiological state (e.g., the received physiological state or aphysiological state other than the received physiological state). Theestimation of blood flow may include, for example, estimated blood flowmagnitude and/or estimated blood flow direction. Anatomical/diseasestates may include, for example, blood flow for the patient in a healthystate or blood flow from an anatomical model of the patient at a priortime (e.g., using a pre-modification patient-specific model or apost-modification patient-specific model). Modifications may includegeometric changes to the patient-specific model and/or changes to ablood flow, for example, opening or closing a vessel lumen in theanatomical model, revascularization in the anatomical model with abypass graft, modifying the simulated physiological state, opening atotal occlusion, etc.

In one embodiment, step 205 may include determining the reference bloodflow using a known and population-based healthy blood flow, a known andpopulation-based diseased blood flow, and/or a patient-specific healthyblood flow. In one embodiment, the known or population-based blood flowsmay include pre-set or standard reference blood flow values. Alternatelyor in addition, known and population-based blood flows may be obtainedusing, for example, machine learning or stored information. In somecases, the machine learning or stored information may be related topatient information so that the reference blood flow is tailored to thepatient.

To explain further, step 205 of determining the reference blood flow mayadditionally include receiving patient information (e.g.,patient-specific information described for FIG. 1B, including patientage, sex, medical history, physiological state, etc.). In oneembodiment, machine learning may include building a collection of bloodflow-related data (e.g., boundary conditions for flow simulations,geometry of modeled anatomy, etc.) pertaining to one or moreindividuals. Machine learning may include iteratively calculating bloodflow using the blood flow-related data, to create simulations thatcharacterize blood flow at a given set of conditions, e.g., patient age,sex, health condition, physiological state, medical history, etc. Inother words, machine learning may provide reliable estimates ofreference blood flow for a particular input, e.g., input for individualssimilar to the patient.

Stored information may include information in a database. Step 205 mayinclude selecting, from a variety of databases, a database containingblood flow information for individuals with characteristics that aresimilar to the received patient information. The database may includeknown (e.g., measured or simulated) examples of the blood flowcharacteristic. Such examples of the blood flow characteristic may beassociated with one or more other patients and/or a population-basedstudy, for example. The simulated examples may be derived from themachine-learning methods described earlier.

A patient-specific healthy blood flow may be obtained, for example, bydetecting and removing disease elements from the patient-specificanatomical model and/or by estimating the patient-specific healthy bloodflow using the patient-specific anatomical model. Estimating thepatient-specific healthy blood flow may include, for instance,performing a 1 D or 3D blood flow simulation, e.g., using a machinelearning technique to estimate blood flow at a location (e.g., using adatabase of blood flow rates from similar healthy patients at similarlocations). For example, the simulation may include using a differentanatomical model of the patient. Examples of such an anatomical modelmay include a modified version of the received patient-specific anatomicmodel, or a model determined prior to the received model (e.g., showingthe patient at a different time or physiological state from the time orphysiological state associated with the received model). Alternately orin addition, the simulation may include using a pre-treatment blood flow(e.g., in which the treatment may be virtual or actual). Furthermore,the simulation may include a physics-based or reduced-order model forsimulating the blood flow (e.g., using computational fluid dynamics).Parameters of the simulation may be adjusted to model blood flow atvarious physiological states.

In one embodiment, step 207 may include receiving an estimate of actualblood flow for the patient at one or more locations in thepatient-specific anatomical model. In one embodiment, step 207 mayinclude receiving an actual patient blood flow by determining anestimate of the patient's actual blood flow rate. For example,estimating the actual flow rate may include measuring the actual flowrate from invasive measurements or noninvasive imaging, performing a 0D,1D or 3D blood flow simulation, using a machine learning technique toestimate blood flow at a location, etc. Invasive measurements mayinclude measurements found using a pressure wire. Noninvasive imagingmay include Doppler ultrasound or magnetic resonance imaging (MRI). Anexemplary machine learning technique may include using a database ofblood flow rates from similar patients, at similar locations of therespective patients' vasculature. In one embodiment, the estimated,actual blood flow rate for the patient may be associated with thereceived physiological state (e.g., from step 203).

In one embodiment, step 209 may include determining, using a processor(e.g., a computer, laptop, tablet, smart phone, digital signalprocessing (DSP), cloud computer, graphics processing unit), acomparison of the patient's actual blood flow rate at a location in thepatient-specific model to the reference blood flow rate at a location ofa vasculature corresponding to the location in the patient-specificmodel. Such a comparison may be made for blood flow at multiplelocations in the patient-specific model. In one embodiment, thecomparison of step 209 may include comparing the blood flow direction(e.g., by determining the inner product velocity vectors) and/or theblood flow magnitude (e.g., by taking an absolute difference or squareddifference) for the reference blood flow rate versus the patient'sactual blood flow rate.

In one embodiment, step 211 may include outputting the comparison to anelectronic storage medium or electronic display. For example, thecomparison may be shown as a graphical, numerical, and/or pictorialdisplay. In one embodiment, the comparison of step 211 may be sufficientto diagnose a steal syndrome or retrograde flow. For instance, step 211may prompt a diagnosis of disease where the difference between thepatient's actual blood flow and the reference blood flow exceeds a giventhreshold.

In another alternate or additional embodiment, the comparison of step211 may include a comparison of relative blood flow, e.g., relativeblood flow magnitude. For example, since step 207 may include receivingan estimate of actual blood flow magnitude for the patient (M_(P)) atone or more locations in the patient-specific anatomical model, oneembodiment of method 200 may include comparing an estimate of patientblood flow magnitude at a first location (e.g., L_(P1)) in the patient'svasculature against an estimate of patient blood flow magnitude at asecond location (e.g., L_(P2)) in the patient's vasculature. The patientblood flow may be characterized as, for instance,

M _(P)=(M _(LP1) M _(LP2))

In such an embodiment, the reference blood flow may also include arelative measurement, e.g., reference blood flow at location (L_(R1))corresponding to the first location (L_(P1)) of the patient'svasculature versus reference blood flow at a location (L_(R2))corresponding to the second location (L_(P2)) of the patient'svasculature. In other words, reference relative blood flow may becharacterized as,

M _(R)=(M _(LR1) M _(LR2))

M_(R) may include the difference in blood flow magnitude between oneselected location in a vasculature versus a second selected location inthe vasculature of a healthy individual. In one embodiment, the relativemeasurement may include a difference in measurements, e.g., as describedabove with M_(P) and M_(R). In another exemplary embodiment, therelative measurement may include a ratio of measurements, e.g., whereM_(P)=(M_(LP1/)M_(LP2)) and M_(R)=(M_(LR1/)M_(LR2)).

A difference between M_(P) and M_(R) may indicate a steal syndrome inthe patient's vasculature. In other words, a patient relative blood flowmagnitude may deviate from an expected or healthy relative blood flowmagnitude because an amount of blood is being “stolen.” Accordingly, acomparison of relative blood flow (or blood flow magnitude) may providea diagnosis for steal syndrome.

For example, a diagnosis for subclavian steal syndrome may includeM_(P)=(M_(LP1) M_(LP2)), where L_(P1) a location in the subclavianartery and L_(P2) a location in the vertebral artery. In such ascenario, vascular steal syndrome may be indicated where M_(P)>M_(R),since subclavian steal syndrome may involve the subclavian arterylocation (L_(P1)) “stealing” blood flow from the vertebral arterylocation (L_(P2)). In another scenario, L_(P1) may be located in thevertebral artery and L_(P2) may be located in the aortic arch,downstream of the vertebral artery. Then, M_(P)<M_(R) may indicatesubclavian steal syndrome, where a magnitude of blood flow through theaortic arch is lower than in a healthy individual, since blood flow isbeing “stolen” by the vertebral artery. The locations L_(P1) and L_(P2)in a vasculature may influence the predetermined relationship orthreshold difference between M_(P) and M_(R) that may be identified ordefined for prompting a diagnosis.

Furthermore, the difference between M_(P) and M_(R), or the ratio,M_(P:)M_(R), may be compared to a threshold value that may be indicativeof steal syndrome. For example, an individual may be healthy ifM_(P:)M_(R)=1, meaning the patient's blood flow matches that of ahealthy, reference blood flow. A ratio greater than 1.3 or less than0.7, for example, may indicate an “unhealthy stealing” of blood from onevessel to another vessel. Threshold values, in such a case, may include,for example, 1.3 as a maximum threshold and 0.7 as a minimum threshold.

In yet another alternate or additional embodiment, method 200 may beperformed for various physiological states so that the output comparison(e.g., from step 211) may be analyzed across a plurality ofphysiological states. In some scenarios, retrograde flow or “stealing”of blood (related to a vascular steal syndrome), for instance, may occuronly in some physiological states. Comparing the output of step 211 formore than one physiological state may permit identification of aphysiological state where a patient may experience retrograde flow or“stealing” of blood. In one embodiment, such information may pertainonly to the patient. Alternately or in addition, such information may beuseful for extrapolating information for a population of individuals,e.g., individuals that may share similar patient characteristics (e.g.,medical history, age, gender, physical condition, etc.). The associationmay permit a recommendation as to physiological states that a patient(or individuals similar to the patient) should be cautious of, or avoid.For example, if the patient blood flow varies drastically from areference blood flow for a patient while the patient engages in rigorousexercise, the association in step 211 may further prompt arecommendation for the patient to try to avoid rigorous exercise.

FIG. 3A is a block diagram of an exemplary method 300 of locating areasof vascular steal syndromes and/or retrograde flow, according to anexemplary embodiment. The method of FIG. 3A may be performed by serversystems 126, based on information, images, and data received fromphysicians 122 and/or third party providers 124 over electronic network121.

As previously discussed, deviant blood flow may include instances ofdiscrepancies between a patient's blood flow and a reference (e.g.,healthy) blood flow. For example, the difference in blood flow directionmay be determined, in an exemplary case, where the inner product of theblood flow rate velocity vector of the reference blood flow rate and thevelocity vector of the actual blood flow rate is less than zero. In somecases, only a subset of the deviant blood flow may be significant fordisease analysis. Method 300 may include isolating, from the comparisonperformed in method 200, a subset of deviant blood flow for diseaseanalysis. In one embodiment, method 300 may include displaying thesubset of deviant blood flow.

In one embodiment, step 301 may include defining a standard or criteriafor the deviant blood flow to display to a user, e.g., a user performingor using such a disease analysis. One standard may include displaying adifference between an actual blood flow magnitude and a reference bloodflow magnitude that exceeds a predetermined threshold (e.g., 1.3 or 0.7,as described for step 207). Another standard may include displaying adifference, between an actual blood flow magnitude and a reference bloodflow magnitude, that may be a statistical outlier among computeddifferences. Similar standards regarding predetermined thresholds orstatistical outliers may apply to relative blood flow magnitudes.

In one embodiment, step 303 may include determining deviant blood flowwithin a patient's vasculature (e.g., from step 207 or step 211) thatmeets a criteria for display and/or disease analysis (e.g., from step301). For example, step 303 may include determining one or morelocations in the patient's vasculature where the difference between thepatient's blood flow magnitude and a reference blood flow magnitude is astatistical outlier among computed differences. Step 303 may furtherinclude determining varying grades or levels of severity in thedeviation between the reference blood flow and the patient blood flow.

In one embodiment, step 305 may include generating a user interfacedisplaying the determined deviant blood flow within the patient'svasculature, e.g., on a representation of the patient-specific model.For example, step 305 may include outputting a display including arepresentation of the patient-specific model, with the areas of deviantblood flow shown (e.g., via highlighting, color, or any type of visualsignifier). In one embodiment, the display or representation generatedin step 305 may also distinguish between varying degrees or extents ofdeviation between the reference blood flow and actual blood flow. Forexample, locations of the patient vasculature that experience highdeviation may be marked yellow in the representation, while locationswith low deviation may be marked as green in the representation. Thedisplay may be output or stored on an electronic medium or electronicdisplay (step 307).

FIG. 3B is a block diagram of an exemplary method 320 of comparingtreatments for vascular steal syndromes and/or retrograde flow,according to an exemplary embodiment. The method of FIG. 3B may beperformed by server systems 126, based on information, images, and datareceived from physicians 122 and/or third party providers 124 overelectronic network 121.

In one embodiment, step 321 may include receiving an input for amodification to the patient-specific model, e.g., a geometricalmodification and/or a physiological state change. Modifications to thepatient-specific model may reflect multiple different treatments ordisease progressions. Exemplary modifications may include, for example,narrowing a portion of vasculature in the patient-specific anatomicmodel at a location to reflect disease progression, modifying a portionof vasculature in the patient-specific model to show varying levels ofblockage at one or more locations in the patient's vasculature toreflect the onset or introduction of an occlusion or resection, wideningthe vascular model at a location to reflect disease regression, wideninga portion of vasculature in the patient-specific anatomic model at alocation in the model to reflect a virtual stent (or other device towiden the vessel), adding one or more additional branches to a portionof vasculature in the patient-specific anatomic model to reflect abypass, etc.

In one embodiment, step 323 may include modifying the patient-specificmodel, based on the received input for the modification. Step 323 mayfurther include generating a representation of the modification and/orprompting a validation or further selection related to the modification.For example, if the modification includes modeling disease progression,step 323 may include generating a prompt for a user to selectlocation(s) of the patient-specific model in which to observe thedisease progression, and generating a further prompt requesting a rangeof time or level of progression to analyze and/or display.

In one embodiment, step 325 may include recalculating patient bloodflow, based on the modifications (e.g., using the modifiedpatient-specific model). The recalculations may be performed using oneor more methods described, for example, at step 207 of method 200. Inone embodiment, step 325 may further include updating reference bloodflows, based on the received modification and/or the recalculation(e.g., to train an algorithm in generating accurate reference blood flowinformation).

In one embodiment, step 327 may include computing a comparison betweenthe patients blood flow pre-modification (e.g., from step 207 of method200), and the patient's blood flow post-modification (e.g., from step325).

In one embodiment, step 329 may include outputting results of thecomparison to, e.g., an electronic storage medium. Such a comparison maybe used for treatment planning. For example, an input may include amodification comprising an introduction of an occlusion or a widening inthe patient's vasculature. One such case may include a modificationintroducing an occlusion at a first location in the patient'svasculature. Another input may include a modification comprising anintroduction of an occlusion at a second location in the patient'svasculature. Blood flow estimates for each of the occlusion locationsmay be compared to reference blood flow rate(s). For example, theocclusion location that results in a patient blood flow with lowerdeviation from the reference blood flow, may be chosen as a treatmentrecommendation over the occlusion location that may cause a patientblood flow with higher deviation from the reference blood flow. Anothercase may include a modification introducing a widening at a firstlocation in the patient's vasculature, and a widening at a secondlocation in the patient's vasculature. Blood flow estimates for each ofthe widened locations may be compared to reference blood flow rate(s),and a location associated with lower deviation from the reference bloodflow may be selected as a treatment site (over locations associated withhigher deviation).

Blood flow that deviates from an expected, healthy blood flow sometimesimpacts a patient health. For example, deviant blood flow may causevascular steal syndromes, which may endanger a patient. Harmful patientconditions related to deviant blood flow may be difficult to detect,since the deviant blood flow may occur only under certain physiologicalstates, or effects of the deviant blood flow may become more pronouncedonly under certain physiological states. The present disclosure may beuseful in detecting deviant blood flow in advance, thus improvingdiagnoses for vascular steal syndromes and/or retrograde flow. Inaddition, a better understanding of deviant flow may improve treatmentplanning, either to better treat vascular steal syndromes and/orretrograde flow or to better select treatments for a patient that areless likely to later induce vascular steal syndromes and/or retrogradeflow.

Other embodiments of the invention will be apparent to those skilled inthe art from consideration of the specification and practice of theinvention disclosed herein. It is intended that the specification andexamples be considered as exemplary only, with a true scope and spiritof the invention being indicated by the following claims.

1-20. (canceled)
 21. A computer-implemented method of determining bloodflow deviation in a patient's vasculature, the method comprising:receiving a reference vasculature and a patient's vasculature of atleast a common anatomical region; receiving (1) a first reference bloodflow magnitude indicating an amount of blood flow at a predeterminedfirst location in a reference vasculature, and (2) a second referenceblood flow magnitude indicating an amount of blood flow at apredetermined second location in the reference vasculature, the secondlocation being a location outside of an expected direction of bloodflow; calculating a reference relative blood flow magnitude by comparingthe first reference blood flow magnitude to the second reference bloodflow magnitude; receiving a first location and a second location in apatient's vasculature, wherein the patient's vasculature and thereference vasculature are of at least a common anatomical region, andwherein the first and second locations in the patient's vasculaturecorrespond to the predetermined first and predetermined second locationsin the reference vasculature, respectively; determining, non-invasively,(1) a first patient-related blood flow magnitude indicating an amount ofblood flow at the first location in a patient's vasculature, and (2) asecond patient-related blood flow magnitude indicating an amount ofblood flow at the second location in the patient's vasculature;determining a patient-related relative blood flow magnitude by comparingthe non-invasively determined first patient-related blood flow magnitudeto the non-invasively determined second patient-related blood flowmagnitude; determining a difference or ratio between the referencerelative blood flow magnitude and the patient-related relative bloodflow magnitude, based on a comparison of the reference relative bloodflow magnitude and the patient-related relative blood flow magnitude;and generating, to an electronic storage medium or display by an imageprocessor, (1) an anatomical representation of the patient's vasculaturebased on the determined difference or ratio between the referencerelative blood flow magnitude and the patient-related relative bloodflow magnitude, and (2) an optimal treatment recommendation for thepatient's vasculature for reducing the determined difference or ratio,if the determined difference or ratio between the reference relativeblood flow magnitude and the patient-related relative blood flowmagnitude indicates vascular steal syndrome, wherein the treatmentrecommendation includes a location of vascular steal, and ensures thatthe treatment does not cause further vascular steal syndrome as abyproduct.
 22. The computer-implemented method of claim 21, furthercomprising: receiving a physiological state associated with the patient;receiving the reference relative blood flow magnitude based on thephysiological state; and determining the patient-related relative bloodflow magnitude based on the physiological state.
 23. Thecomputer-implemented method of claim 21, further comprising: receiving apatient-specific anatomic model of the patient's vasculature; anddetermining the patient-related relative blood flow magnitude bysimulating or estimating blood flow through locations in thepatient-specific anatomic model corresponding to the first location inthe reference vasculature and the second location in the referencevasculature.
 24. The computer-implemented method of claim 23, furthercomprising: determining one or more areas of the patient-specificanatomic model associated with the difference between the referencerelative blood flow magnitude and the patient-related relative bloodflow magnitude; and generating the anatomical representation based onthe one or more areas of the patient-specific anatomic model associatedwith the difference between the reference relative blood flow magnitudeand the patient-related relative blood flow magnitude.
 25. Thecomputer-implemented method of claim 21, further comprising: determininga second patient-related relative blood flow magnitude from asimulation; and comparing the reference relative blood flow magnitude tothe second patient-related relative blood flow magnitude to determine adifference between the reference relative blood flow magnitude and thesecond patient-related relative blood flow magnitude.
 26. Thecomputer-implemented method of claim 25, further comprising: generatingthe treatment recommendation further based on a comparison of thedifference between the reference relative blood flow magnitude and thepatient-related relative blood flow magnitude against the differencebetween the reference relative blood flow magnitude and the secondpatient-related relative blood flow magnitude.
 27. Thecomputer-implemented method of claim 25, wherein the simulation for thesecond patient-related relative blood flow magnitude includes a vasculargeometry different from the geometry of the patient's vasculature or aphysiological state different from the physiological state at which thepatient-related relative blood flow magnitude is determined.
 28. Thecomputer-implemented method of claim 21, wherein the treatmentrecommendation is for diseases other than vascular steal syndrome.
 29. Asystem for determining blood flow deviation in a patient's vasculature,the system comprising: at least one data storage device storinginstructions for determining blood flow deviation in a patient'svasculature; and at least one processor configured to execute theinstructions to perform operations including: receiving a referencevasculature and a patient's vasculature of at least a common anatomicalregion; receiving (1) a first reference blood flow magnitude indicatingan amount of blood flow at a predetermined first location in a referencevasculature, and (2) a second reference blood flow magnitude indicatingan amount of blood flow at a predetermined second location in thereference vasculature, the second location being a location outside ofan expected direction of blood flow; calculating a reference relativeblood flow magnitude by comparing the first reference blood flowmagnitude to the second reference blood flow magnitude; receiving afirst location and a second location in a patient's vasculature, whereinthe patient's vasculature and the reference vasculature are of at leasta common anatomical region, and wherein the first and second locationsin the patient's vasculature correspond to the predetermined first andpredetermined second locations in the reference vasculature,respectively; determining, non-invasively, (1) a first patient-relatedblood flow magnitude indicating an amount of blood flow at the firstlocation in a patient's vasculature, and (2) a second patient-relatedblood flow magnitude indicating an amount of blood flow at the secondlocation in the patient's vasculature; determining a patient-relatedrelative blood flow magnitude by comparing the non-invasively determinedfirst patient-related blood flow magnitude to the non-invasivelydetermined second patient-related blood flow magnitude; determining adifference or ratio between the reference relative blood flow magnitudeand the patient-related relative blood flow magnitude, based on acomparison of the reference relative blood flow magnitude and thepatient-related relative blood flow magnitude; and generating, to anelectronic storage medium or display by an image processor, (1) ananatomical representation of the patient's vasculature based on thedetermined difference or ratio between the reference relative blood flowmagnitude and the patient-related relative blood flow magnitude, and (2)an optimal treatment recommendation for the patient's vasculature forreducing the determined difference or ratio, if the determineddifference or ratio between the reference relative blood flow magnitudeand the patient-related relative blood flow magnitude indicates vascularsteal syndrome, wherein the treatment recommendation includes a locationof vascular steal, and ensures that the treatment does not cause furthervascular steal syndrome as a byproduct.
 30. The system of claim 29, theoperations further comprising: receiving a physiological stateassociated with the patient; receiving the reference relative blood flowmagnitude based on the physiological state; and determining thepatient-related relative blood flow magnitude based on the physiologicalstate.
 31. The system of claim 29, the operations further comprising:receiving a patient-specific anatomic model of the patient'svasculature; and determining the patient-related relative blood flowmagnitude by simulating or estimating blood flow through locations inthe patient-specific anatomic model corresponding to the first locationin the reference vasculature and the second location in the referencevasculature.
 32. The system of claim 31, the operations furthercomprising: determining one or more areas of the patient-specificanatomic model associated with the difference between the referencerelative blood flow magnitude and the patient-related relative bloodflow magnitude; and generating the anatomical representation based onthe one or more areas of the patient-specific anatomic model associatedwith the difference between the reference relative blood flow magnitudeand the patient-related relative blood flow magnitude.
 33. The system ofclaim 29, the operations further comprising: determining a secondpatient-related relative blood flow magnitude from a simulation; andcomparing the reference relative blood flow magnitude to the secondpatient-related relative blood flow magnitude to determine a differencebetween the reference relative blood flow magnitude and the secondpatient-related relative blood flow magnitude.
 34. The system of claim33, wherein the simulation for the second patient-related relative bloodflow magnitude includes a vascular geometry different from the geometryof the patient's vasculature or a physiological state different from thephysiological state at which the patient-related relative blood flowmagnitude is determined.
 35. A non-transitory computer readable mediumfor use on a computer system containing computer-executable programminginstructions for performing operations determining blood flow deviationin a patient's vasculature, the operations comprising: receiving areference vasculature and a patient's vasculature of at least a commonanatomical region; receiving (1) a first reference blood flow magnitudeindicating an amount of blood flow at a predetermined first location ina reference vasculature, and (2) a second reference blood flow magnitudeindicating an amount of blood flow at a predetermined second location inthe reference vasculature, the second location being a location outsideof the expected direction of blood flow; calculating a referencerelative blood flow magnitude by comparing the first reference bloodflow magnitude to the second reference blood flow magnitude; receiving afirst location and a second location in a patient's vasculature, whereinthe patient's vasculature and the reference vasculature are of at leasta common anatomical region, and wherein the first and second locationsin the patient's vasculature correspond to the predetermined first andpredetermined second locations in the reference vasculature,respectively; determining, non-invasively, (1) a first patient-relatedblood flow magnitude indicating an amount of blood flow at the firstlocation in a patient's vasculature, and (2) a second patient-relatedblood flow magnitude indicating an amount of blood flow at the secondlocation in the patient's vasculature; determining a patient-relatedrelative blood flow magnitude by comparing the non-invasively determinedfirst patient-related blood flow magnitude to the non-invasivelydetermined second patient-related blood flow magnitude; determining adifference or ratio between the reference relative blood flow magnitudeand the patient-related relative blood flow magnitude, based on acomparison of the reference relative blood flow magnitude and thepatient-related relative blood flow magnitude; and generating, to anelectronic storage medium or display by an image processor, (1) ananatomical representation of the patient's vasculature based on thedetermined difference or ratio between the reference relative blood flowmagnitude and the patient-related relative blood flow magnitude, and (2)an optimal treatment recommendation for the patient's vasculature forreducing the determined difference or ratio, if the determineddifference or ratio between the reference relative blood flow magnitudeand the patient-related relative blood flow magnitude indicates vascularsteal syndrome, wherein the treatment recommendation includes a locationof vascular steal, and ensures that the treatment does not cause furthervascular steal syndrome as a byproduct.
 36. The computer-readable mediumof claim 35, the operations further comprising: receiving aphysiological state associated with the patient; receiving the referencerelative blood flow magnitude based on the physiological state; anddetermining the patient-related relative blood flow magnitude based onthe physiological state.
 37. The computer-readable medium of claim 35,the operations further comprising: receiving a patient-specific anatomicmodel of the patient's vasculature; and determining the patient-relatedrelative blood flow magnitude by simulating or estimating blood flowthrough locations in the patient-specific anatomic model correspondingto the first location in the reference vasculature and the secondlocation in the reference vasculature.
 38. The computer-readable mediumof claim 37, the operations further comprising: determining one or moreareas of the patient-specific anatomic model associated with thedifference between the reference relative blood flow magnitude and thepatient-related relative blood flow magnitude; and generating theanatomical representation based on the one or more areas of thepatient-specific anatomic model associated with the difference betweenthe reference relative blood flow magnitude and the patient-relatedrelative blood flow magnitude.
 39. The computer-readable medium of claim35, the operations further comprising: determining a secondpatient-related relative blood flow magnitude from a simulation; andcomparing the reference relative blood flow magnitude to the secondpatient-related relative blood flow magnitude to determine a differencebetween the reference relative blood flow magnitude and the secondpatient-related relative blood flow magnitude.
 40. The computer-readablemedium of claim 39, wherein the simulation for the secondpatient-related relative blood flow magnitude includes a vasculargeometry different from the geometry of the patient's vasculature or aphysiological state different from the physiological state at which thepatient-related relative blood flow magnitude is determined.